For the past decade we have carried out systematic studies of humoral and cellular immunity in patients with primary immunodeficiency syndromes. Antibody formation has been assessed using bacteriophage phiX 174 as antigen. Lymphocyte function has been evaluated by response to a standardized battery of mitogens; B and T cell lines have been enumerated by rosette formation and immunofluorescence. Similar studies have been carried out on human bone marrow transplantation chimeras. We now plan to assess in vitro immunoglobulin and antibody synthesis of B cells to determine actual rates of production, to evaluate the quality (affinity) of antibody as well as amount, and to explore the control mechanisms involved. Both in vitro and in vivo studies will be carried out. Attempts will be made to reconstitute effective immune function with new therapeutic approaches including transplants of fetal tissue, cell extracts (transfer factor) and thymus extracts (thymosin). These studies relate to basic and clinical immunobiology, including resistance to infection, development of malignancy, allergy, and collagen diseases.